PB1898: BONE MARROW APLASIA – A RARE COMPLICATION OF IMATINIB THERAPY IN CML PATIENTS: ABOUT A CASE
Authors: W. chawad, S. fari firdaous, F. Ibourk Idrissi, S. belkhettab, A. taouch, H. khibri, N. mouatassim, W. ammouri, M. maamar, H. harmouche, Z. Mezalek Tazi, M. adnaoui
Journal: HemaSphere (2022)

Background: Chronic myeloid leukemia (CML) belongs to the family of myeloproliferative neoplasms. Tyrosine kinase inhibitors (TKIs) constitute the reference therapeutic family. They have revolutionized the future of patients because of their ability to prevent, in the majority of cases, the once inevitable progression of CML into fatal acute leukemia. Imatinib, a 1st generation TKI, is a drug that is generally well tolerated in the majority of patients. However, a significant number of hematological complications has been reported. Aims: TKI-induced bone marrow aplasia is a rarely described complication of TKI. We wanted to highlight this poorly recognized entity. Methods: We report the case of a patient with CML, who developed severe bone marrow failure after treatment with Imatinib. Results: A 25-year-old man presented himself to the emergency in October 2019. He reports fatigue, weight loss, fever and heaviness in the left hypochondrium. Physical examination noted the presence of cutaneous pallor associated with splenomegaly. Biologically, we found a hyperleukocytosis at 74 giga made up of neutrophils (66 giga), anemia at 5g/dl and a thrombocytosis at 669 giga. The blood smear showed a harmonious myelemia with blasts at 4% rate. The initial analysis of the bown marrow aspirate showed a myeloid hyperplasia at 82% with a blast rate of 1%. The diagnosis of CML was confirmed by the presence of the Philadelphia chromosome and the detection of the bcr-abl fusion transcript at 86%. The patient initially received cytoreductive treatment based on hydroxyurea for 1 week before the introduction of imatinib at a dose of 400 mg/day. One month after, the splenomegaly reduced and the blood count showed a neutropenia at 900, which leaded initialy to an adaptation of the doses of imatinib to 300 mg / day and resuming after that to the optimal dose. Six months after the initiation of the TKI at 400 mg/day, the patient presented a severe bone marrow failure. The blood count found a non regenerative pancytopenia with hemoglobin at 5g/dl, agranulocytosis at 40 elements/mm3 with thrombocytopenia at 6000/mm3 leading to definitive discontinuation of imatinib. The bown marrow aspirate was poor. On karyotype, all mitoses still presented the Phi chromosome. The osteo-medullary biopsy revealed a medullary hypoplasia. In the absence of an HLA-compatible donor and antilymphocyte serum, the patient was treated with thrombopoeitin analogs at a dose of 2 ug/week along with transfusion support, witch showed a good clinical and biological evolution.His last blood count is strictly normal and he has not been transfused in the last 6 months. Summary/Conclusion: TKIs have revolutionized the treatment of CML. In fact, most of imatinib side effects are moderate and subside over time. However, ITK can also lead to rare complications, such as bone marrow failure. Clinical and hematological monitoring with the study of bone marrow apirate will be required at regular intervals for the early recognition of this phenomenon. Patients will be referred early to an allograft of bone marrow,thus avoiding the fatal consequences of sepsis due to neutropenia or hemorrhage on severe thrombocytopenia